Original Report: Laboratory Investigation

Direct Injection of Calcitriol or Its Analog Improves Abnormal Gene Expression in the Hyperplastic Parathyroid Gland in Uremia
Kazuhiro Shiizaki^a, Masafumi Fukagawa^b, Qunsheng Yuan^f, Ikuji Hatamura^c, Tomoko Nii-Kono^b, Fumie Saji^d, Takashi Shigematsu^d, Tadao Akizawa<sup>e

a</sup>Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke,
^bDivision of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe,
^cThe First Department of Pathology and
^dDivision of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, and
^eDepartment of Nephrology, Showa University School of Medicine, Showa, Japan;
^fDivision of Nephrology, Peking Union Medical College Hospital, Beijing, China

Address of Corresponding Author

Am J Nephrol 2008;28:59-66 (DOI: 10.1159/000109240)

  Key Words

• Gene
• Hyperparathyroidism
• Nephrectomy, 5/6
• Polymerase chain reaction, real-time
• Vitamin D
• Vitamin D metabolite

  Abstract

Aims: In this study, we investigated the effects of direct injection (DI) of calcitriol or maxacalcitol into the hyperplastic parathyroid gland (PTG) on altered gene expression related to the advanced status of secondary hyperparathyroidism (SHPT). Methods: Sprague-Dawley rats were 5/6-nephrectomized (uremic) or sham-operated (normal). In each uremic rat, one of the bilateral PTG was treated by DI of calcitriol (PTG_CAL) or maxacalcitol (PTG_OCT), and the other gland was treated with control solution (PTG_CONT). The PTG were evaluated for levels of expression of various mRNA and immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Results: Significant differences in levels of expression of mRNA and PCNA were confirmed between the uremic and normal groups. In PTG_CAL and PTG_OCT, expressions of almost all mRNA and PCNA were significantly improved; both agents were able to normalize the abnormalities of the uremic PTG, in contrast to the baseline and individual PTG_CONT. However, the difference in effect between PTG_CAL and PTG_OCT was only small. Conclusion: Our results suggest that very high concentrations of calcitriol or maxacalcitol in the PTG improve abnormal gene expression and proliferation activity of parathyroid cells, and might explain the better control of SHPT using the DI technique.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Kazuhiro Shiizaki, MD, PhD
Division of Nephrology, Department of Internal Medicine, Jichi Medical University
3311-1 Yakushiji, Shimotsuke
Tochigi 329-0498 (Japan)
Tel. +81 285 58 7346, Fax +81 285 44 4869, E-Mail shiizaki@jichi.ac.jp

  Article Information

Part of this study was presented at the Annual Meeting of the American Society of Nephrology held in Philadelphia, Pennsylvania, USA, 2005, and has been punblished as an abstract (J Am Soc Nephrol 16:494A, 2005).

Received: June 28, 2007
Accepted: August 13, 2007
Published online: September 28, 2007
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 2, Number of References : 16